Acute thrombotic manifestations of coronavirus disease 2019 infection: Experience at a large New York City health care system.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel coronavirus that has typically resulted in upper respiratory symptoms. However, we have encountered acute arterial and venous thrombotic events after COVID-19 infection. Managing acute thrombotic events from the novel virus has presented unprecedented challenges during the COVID-19 pandemic. In our study, we have highlighted the unique treatment required for these patients and discussed the role of anticoagulation for patients diagnosed with COVID-19. METHODS: The data from 21 patients with laboratory-confirmed COVID-19 disease and acute venous or arterial thrombosis were collected. The demographics, comorbidities, home medications, laboratory markers, and outcomes were analyzed. The primary postoperative outcome of interest was mortality, and the secondary outcomes were primary patency and morbidity. To assess for significance, a univariate analysis was performed using the Pearson χ2 and Fisher exact tests for categorical variables and the Student t test for continuous variables. RESULTS: A total of 21 patients with acute thrombotic events met our inclusion and exclusion criteria. Most cases were acute arterial events (76.2%), with the remainder venous cases (23.8%). The average age for all patients was 64.6 years, and 52.4% were male. The most prevalent comorbidity in the group was hypertension (81.0%). Several markers were markedly abnormal in both arterial and venous cases, including an elevated neutrophil/lymphocyte ratio (8.8) and D-dimer level (4.9 µg/mL). Operative intervention included percutaneous angiography in 25.00% of patients and open surgical embolectomy in 23.8%. Most of the patients who had undergone arterial intervention had developed a postoperative complication (53.9%) compared with a 0% complication rate after venous interventions. Acute kidney injury on admission was a factor in 75.0% of those who died vs 18.2% in the survivors (P = .04). CONCLUSIONS: We have described our experience in the epicenter of the pandemic of 21 patients who had experienced major thrombotic events from infection with COVID-19. The findings from our cohort have highlighted the need for increased awareness of the vascular manifestations of COVID-19 and the important role of anticoagulation for these patients. More data are urgently needed to optimize treatment and prevent further vascular complications of COVID-19 infections.

Managing central venous access during a health care crisis.

OBJECTIVE: During the COVID-19 pandemic, central venous access line teams were implemented at many hospitals throughout the world to provide access for critically ill patients. The objective of this study was to describe the structure, practice patterns, and outcomes of these vascular access teams during the COVID-19 pandemic. METHODS: We conducted a cross-sectional, self-reported study of central venous access line teams in hospitals afflicted with the COVID-19 pandemic. To participate in the study, hospitals were required to meet one of the following criteria: development of a formal plan for a central venous access line team during the pandemic; implementation of a central venous access line team during the pandemic; placement of central venous access by a designated practice group during the pandemic as part of routine clinical practice; or management of an iatrogenic complication related to central venous access in a patient with COVID-19. RESULTS: Participants from 60 hospitals in 13 countries contributed data to the study. Central venous line teams were most commonly composed of vascular surgery and general surgery attending physicians and trainees. Twenty sites had 2657 lines placed by their central venous access line team or designated practice group. During that time, there were 11 (0.4%) iatrogenic complications associated with central venous access procedures performed by the line team or group at those 20 sites. Triple lumen catheters, Cordis (Santa Clara, Calif) catheters, and nontunneled hemodialysis catheters were the most common types of central venous lines placed by the teams. Eight (14%) sites reported experience in placing central venous lines in prone, ventilated patients with COVID-19. A dedicated line cart was used by 35 (59%) of the hospitals. Less than 50% (24 [41%]) of the participating sites reported managing thrombosed central lines in COVID-19 patients. Twenty-three of the sites managed 48 iatrogenic complications in patients with COVID-19 (including complications caused by providers outside of the line team or designated practice group). CONCLUSIONS: Implementation of a dedicated central venous access line team during a pandemic or other health care crisis is a way by which physicians trained in central venous access can contribute their expertise to a stressed health care system. A line team composed of physicians with vascular skill sets provides relief to resource-constrained intensive care unit, ward, and emergency medicine teams with a low rate of iatrogenic complications relative to historical reports. We recommend that a plan for central venous access line team implementation be in place for future health care crises.

Iliac Remote Endarterectomy to Restore Circulation in a Patient with Infected Aorto-Femoral and Axillo-Bifemoral Bypasses.

We report a case of a patient who underwent a 2-stage operation that included a right obturator bypass with left iliac remote endarterectomy followed by removal of an infected, previously failed aorto-right-femoral and right axillo-bifemoral bypass reconstructions.

Clinical significance of reversal of flow in the vertebral artery identified on cerebrovascular duplex ultrasound.

BACKGROUND: Reversal of flow in the vertebral artery (RFVA) is an uncommon finding on cerebrovascular duplex ultrasound examination. The clinical significance of RFVA and the natural history of patients presenting with it are poorly understood. Our objective was to better characterize the symptoms and outcomes of patients presenting with RFVA. METHODS: A retrospective review was performed of all cerebrovascular duplex ultrasound studies performed at our institution between January 2010 and January 2016 (N = 2927 patients). Individuals with RFVA in one or both vertebral arteries were included in the analysis. RESULTS: Seventy-four patients (74/2927 patients [2.5%]) with RFVA were identified. Half of the patients were male. Mean age at the time of the first ultrasound study demonstrating RFVA was 71 years (range, 27-92 years); 78% of patients had hypertension, 28% were diabetic, and 66% were current or former smokers. Indications for the ultrasound examination were as follows: 44% screening/asymptomatic, 7% anterior circulation symptoms, 20% posterior circulation symptoms, 28% follow-up studies after cerebrovascular intervention, and 5% upper extremity symptoms. At the time of the initial ultrasound examination, 21 patients (28%) had evidence of a prior carotid intervention (carotid endarterectomy or carotid stenting), 21 patients had evidence of moderate (50%-79%) carotid artery stenosis (CAS) in at least one carotid artery, and 12 patients (16%) had evidence of severe (>80%) CAS. Of the 15 patients presenting with posterior circulation symptoms, 11 (73%) had evidence of concomitant CAS. In contrast, 22 of the 59 patients (37%) without posterior circulation symptoms had duplex ultrasound findings of CAS (P = .01). The mean duration of follow-up was 28 ± 22 months. Follow-up data were available for 63 patients (85%), including the 15 patients who presented with posterior circulation symptoms. Of these 15 patients, 5 underwent subclavian artery revascularization, including balloon angioplasty and stenting in 4 patients and open/hybrid revascularization in 1 patient. Five individuals were awaiting intervention. Three patients underwent carotid endarterectomy for CAS, with resultant improvement in posterior circulation symptoms. Finally, one patient was deemed too high risk for intervention, and one patient was found to have an alternative cause for symptoms. The remaining 59 patients continued to be asymptomatic during follow-up. One patient progressed to vertebral artery occlusion, and six patients had progression of CAS. CONCLUSIONS: Symptomatic RFVA responds well to intervention, including subclavian artery stenting and carotid intervention in patients with CAS. The majority of patients with this finding are asymptomatic at the time of presentation. Although progression of vertebral artery disease is rare, these patients may benefit from monitoring for progression of CAS with surveillance ultrasound.

The Transradial Approach for Lower Extremity Vascular Intervention.

Simultaneous technological advancements in both imaging as well as devices have resulted in an expansion of endovascular options for vascular access. In particular, radial access has traditionally been more favored for coronary interventions; its use in the aortoiliac and lower extremity vasculature has been constrained by the length of devices and the size of sheaths required. However, with increasing catheter shaft lengths, in addition to new thin-walled sheaths allowing for downsizing, the ability to perform transradial interventions on infrainguinal and infrageniculate vessels has been more readily facilitated. In this review, we analyze the potential for transradial therapies in the treatment of peripheral arterial disease (PAD).

Contemporary outcomes of surgical revascularization of the lower extremity in patients on dialysis.

OBJECTIVE: Peripheral arterial disease is a common comorbidity found in up to 38% of patients with end-stage renal disease (ESRD). With an increase in the survival rate of patients with ESRD by >25%, there is a lack of contemporary data on the safety of open surgical revascularization of the lower extremity (OSRLE) in this population of patients. We sought to identify the perioperative morbidity and mortality and independent risk factors of mortality in dialysis patients undergoing OSRLE. METHODS: We reviewed data from 34,941 patients who underwent OSRLE from January 2011 to December 2014 at all hospitals in North America participating in the National Surgical Quality Improvement Program (NSQIP). Trauma, emergencies, aneurysms, and endovascular cases were excluded. We compared the 30-day outcomes of 1623 patients on dialysis with those of 33,318 patients not on dialysis. RESULTS: Patients on dialysis were younger (66.0 vs 66.7; P < .01), were more likely to be treated for critical limb ischemia (49.7% vs 33.1%; P < .01), and had more comorbidities compared with patients not on dialysis. Dialysis patients had higher mortality (7.8% vs 2.1%; P < .01) and postoperative complication rates after OSRLE, including myocardial infarction (3.5% vs 1.4%; P < .01), return to the operating room (6.1% vs 2.8%; P < .01), and unplanned readmission (5.2% vs 2.9%; P < .01). Although 30-day patency was not different (0.4% vs 0.4%; P = .56) between the two study groups, major amputation rate was threefold higher in dialysis patients (1.7% vs 0.57%; P < .01). In addition, we identified multiple risk factors that predispose dialysis patients to worse outcome after OSRLE, including older age, African American race, and congestive heart failure. In a subgroup analysis by procedure, dialysis patients who underwent aortobifemoral bypass carried the highest mortality risk (25% vs 3.6%; P < .01). Dialysis patients had higher rates of unplanned reoperation (7.9% vs 3.9%; P < .01) and unplanned readmission (6.2% vs 3.7%; P < .01) and increased length of stay (67.5% vs 47.3%; P < .01) after femoral-distal bypass. CONCLUSIONS: With improvements in the medical care of ESRD patients resulting in a large increase in survival rates, little is known about how dialysis patients fare after OSRLE in the contemporary period. Our study shows that despite advances in the medical management of dialysis patients, improvements in outcomes after revascularization have not yet been realized. We found that specific clinical and procedural factors increase the risk for inferior results. Careful selection of dialysis patients suitable for OSRLE according to these risk factors may improve the management of this still high-risk vascular population.

Novel association between bone mineral density scores and the prevalence of peripheral artery disease in both sexes.

The purpose of the current study was to investigate the association between bone mineral density (BMD) scores and the prevalence of peripheral artery disease (PAD) in a large cohort of subjects who underwent arterial Doppler assessments and calcaneal bone densitometry. The study was performed using data obtained from Life Line Screening Inc. Subjects were self-selected and paid for screening tests. The prevalence of PAD was significantly higher in men with osteopenia (4.5%) and osteoporosis (10.9%) compared to men with normal BMD (3.0%) ( p<0.001). Osteopenia (odds ratio (OR) 1.3) and osteoporosis (OR 2.3) were found to be independent risk factors for the presence of PAD in men. The prevalence of PAD was significantly higher in women with osteopenia (4.8%) and osteoporosis (11.8%) compared to women with normal BMD (3.3%) ( p<0.001). Osteopenia (OR 1.15) and osteoporosis (OR 1.8) were found to be independent risk factors for the presence of PAD in women. The current study reports a strong association of abnormal BMD analysis with the prevalence of PAD, which persists even when controlling for age and associated atherosclerotic risk factors. Although the mechanism by which these two disease processes is related is not completely elucidated, the presence of osteoporosis should make clinicians aware of the possibility of occult PAD or associated atherosclerotic disease in appropriate patients.

Iliac Artery-Uretero-Colonic Fistula Presenting as Severe Gastrointestinal Hemorrhage and Hematuria: A Case Report and Review of the Literature.

Arterioenteric fistulas represent an infrequent but potentially fatal cause of gastrointestinal hemorrhage. Patients often present in extremis from shock and sepsis. This mandates a rapid diagnosis so that prompt, potentially life-saving interventions can be performed. We report the case of a 35-year-old man who presented with hematuria and hematochezia secondary to an iliac artery-uretero-colonic fistula that developed years after open common iliac artery aneurysm repair. His condition rapidly progressed to hemorrhagic shock, and he underwent successful endovascular treatment with a covered stent graft as a bridge to definitive open surgery. Subsequently, graft explantation, extra-anatomic arterial bypass, bowel resection, and ureter ligation was undertaken. A summary of the literature on iliac artery-enteric fistulas follows.

Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis.

BACKGROUND: The Ras association domain family 1 (RASSF1) gene is a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, very little is known about the function of RASSF1C both in normal and transformed cells. METHODS: Gene silencing and over-expression techniques were used to modulate RASSF1C expression in human breast cancer cells. Affymetrix-microarray analysis was performed using T47D cells over-expressing RASSF1C to identify RASSF1C target genes. RT-PCR and western blot techniques were used to validate target gene expression. Cell invasion and apoptosis assays were also performed. RESULTS: In this article, we report the effects of altering RASSF1C expression in human breast cancer cells. We found that silencing RASSF1C mRNA in breast cancer cell lines (MDA-MB231 and T47D) caused a small but significant decrease in cell proliferation. Conversely, inducible over-expression of RASSF1C in breast cancer cells (MDA-MB231 and T47D) resulted in a small increase in cell proliferation. We also report on the identification of novel RASSF1C target genes. RASSF1C down-regulates several pro-apoptotic and tumor suppressor genes and up-regulates several growth promoting genes in breast cancer cells. We further show that down-regulation of caspase 3 via overexpression of RASSF1C reduces breast cancer cells' sensitivity to the apoptosis inducing agent, etoposide. Furthermore, we found that RASSF1C over-expression enhances T47D cell invasion/migration in vitro. CONCLUSION: Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells.

Accuracy of Transcutaneous CO2 Values Compared With Arterial and Capillary Blood Gases.

BACKGROUND: Transcutaneous monitors are utilized to monitor a patient's respiratory status. Some patients have similar values when comparing transcutaneous carbon dioxide (PtcCO2 ) values with blood gas analysis, whereas others show extreme variability. A retrospective review of data was performed to determine how accurately PtcCO2 correlated with CO2 values obtained by arterial blood gas (ABG) or capillary blood gas. METHODS: To determine whether PtcCO2 values correlated with ABG or capillary blood gas values, subjects' records were retrospectively reviewed. Data collected included the PtcCO2 value at the time of blood gas procurement and the ABG or capillary blood gas PCO2 value. Agreement of pairs of methods (ABG vs PtcCO2 and capillary blood gas vs PtcCO2 ) was assessed with the Bland-Altman approach with limits of agreement estimated with a mixed model to account for serial measurements per subject. RESULTS: A total of 912 pairs of ABG/PtcCO2 values on 54 subjects and 307 pairs of capillary blood gas/PtcCO2 values on 34 subjects were analyzed. The PCO2 range for ABG was 24-106 mm Hg, and PtcCO2 values were 27-133 mm Hg. The PCO2 range for capillary blood gas was 29-108 mm Hg, and PtcCO2 values were 30-103 mm Hg. For ABG/PtcCO2 comparisons, the Pearson correlation coefficient was 0.82, 95% CI was 0.80-0.84, and P was <.001. For capillary blood gas/PtcCO2 comparisons, the Pearson correlation coefficient was 0.77, 95% CI was 0.72-0.81, and P was <.001. For ABG/PtcCO2 , the estimated difference ± SD was -6.79 ± 7.62 mm Hg, and limits of agreement were -22.03 to 8.45. For capillary blood gas/PtcCO2 , the estimated difference ± SD was -1.61 ± 7.64 mm Hg, and limits of agreement were -16.88 to 13.66. The repeatability coefficient was about 30 mm Hg. CONCLUSIONS: Based on these data, capillary blood gas comparisons showed less variation and a slightly lower correlation with PtcCO2 than did ABG comparisons. After accounting for serial measurements per patient, due to the wide limits of agreement and poor repeatability, the utility of relying on PtcCO2 readings for this purpose is questionable.

The Warrington workload tool: determining its use in one trust.

With recent advances in chronic disease management and with earlier discharge from the acute sector, it has become increasingly important for district nurses to monitor and evidence their increasing workload, to monitor demand and capacity. The district nursing service in the author's trust has employed an adaptation of the Warrington workload tool, over several years, to demonstrate and evidence their workload. However, many dispute the accuracy of such tools. This audit set out to discover how accurately the tool was being calculated. The findings have cast doubt on the tool's accurate completion and highlighted an ongoing training need to ensure improvement in its use. The tool is to be further supported with the inclusion of a caseload profiling tool to provide qualitative evidence of the service that the nurses now provide. It was also identified that the service needs evidence that their resource needs are met in response to workload tool data to ensure the tool continues to be used in a proactive manner.

Vascular control for a forequarter amputation of a massive fungating humeral osteosarcoma.

Forequarter amputation is a radical operation performed for treatment of malignant neoplasms of the shoulder girdle not amenable to limb salvage. Traditional approaches involve bone and soft tissue resection, followed by ligation of the axillary vessels. We describe a technique to minimize blood loss whereby control of the subclavian vessels is performed before amputation of a large tumor associated with extensive venous congestion. A 34-year-old man presented with proximal humeral osteosarcoma. Surgery involved claviculectomy to facilitate vascular control of the subclavian vessels, followed by guillotine amputation at the proximal upper arm level and completion of the amputation as conventionally described.

Study of therapeutic hypothermia (32 to 35°C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial): outcome of the pilot phase of the trial.

BACKGROUND: Clinical trials in traumatic brain injury (TBI) are challenging. Previous trials of complex interventions were conducted in high-income countries, reported long lead times for site setup and low screened-to-recruitment rates.In this report we evaluate the internal pilot phase of an international, multicentre TBI trial of a complex intervention to assess: design and implementation of an online case report form; feasibility of recruitment (sites and patients); feasibility and effectiveness of delivery of the protocol. METHODS: All aspects of the pilot phase of the trial were conducted as for the main trial. The pilot phase had oversight by independent Steering and Data Monitoring committees. RESULTS: Forty sites across 12 countries gained ethical approval. Thirty seven of 40 sites were initiated for recruitment. Of these, 29 had screened patients and 21 randomized at least one patient. Lead times to ethics approval (6.8 weeks), hospital approval (18 weeks), interest to set up (61 weeks), set up to screening (11 weeks), and set up to randomization (31.6 weeks) are comparable with other international trials. Sixteen per cent of screened patients were eligible. We found 88% compliance rate with trial protocol. CONCLUSION: The pilot data demonstrated good feasibility for this large international multicentre randomized controlled trial of hypothermia to control intracranial pressure. The sample size was reduced to 600 patients because of homogeneity of the patient group and we showed an optimized cooling intervention could be delivered. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN34555414.

RASSF1C modulates the expression of a stem cell renewal gene, PIWIL1.

BACKGROUND: RASSF1A and RASSF1C are two major isoforms encoded by the Ras association domain family 1 (RASSF1) gene through alternative promoter selection and mRNA splicing. RASSF1A is a well established tumor suppressor gene. Unlike RASSF1A, RASSF1C appears to have growth promoting actions in lung cancer. In this article, we report on the identification of novel RASSF1C target genes in non small cell lung cancer (NSCLC). METHODS: Over-expression and siRNA techniques were used to alter RASSF1C expression in human lung cancer cells, and Affymetrix-microarray study was conducted using NCI-H1299 cells over-expressing RASSF1C to identify RASSF1C target genes. RESULTS: The microarray study intriguingly shows that RASSF1C modulates the expression of a number of genes that are involved in cancer development, cell growth and proliferation, cell death, and cell cycle. We have validated the expression of some target genes using qRT-PCR. We demonstrate that RASSF1C over-expression increases, and silencing of RASSF1C decreases, the expression of PIWIL1 gene in NSCLC cells using qRT-PCR, immunostaining, and Western blot analysis. We also show that RASSF1C over-expression induces phosphorylation of ERK1/2 in lung cancer cells, and inhibition of the MEK-ERK1/2 pathway suppresses the expression of PIWIL1 gene expression, suggesting that RASSF1C may exert its activities on some target genes such as PIWIL1 through the activation of the MEK-ERK1/2 pathway. Also, PIWIL1 expression is elevated in lung cancer cell lines compared to normal lung epithelial cells. CONCLUSIONS: Taken together, our findings provide significant data to propose a model for investigating the role of RASSF1C/PIWIL1 proteins in initiation and progression of lung cancer.

Top2 SUMO conjugation in yeast cell lysates.

DNA topoisomerase II (Topo II), named Top2 in budding and fission yeast, is a conserved target of the SUMO modification pathway, with SUMO-conjugated forms of Topo II accumulating specifically during mitosis in both yeast and vertebrate cells (Bachant et al., Mol Cell 9, 1169-82, 2002; Azuma et al., J Cell Biol 163, 477-87, 2003; Dawlaty et al., Cell 133, 103-15, 2008). As with many SUMO substrates, the functional significance of this modification is still incompletely understood and, perhaps surprisingly, better characterized in vertebrates than yeasts. It seems likely, however, that continued analysis of yeast Top2 SUMO modification will reveal commonalities with vertebrate cells, leading to a deeper understanding of how sumoylation regulates Topo II function. Toward this end, we describe a protocol for analyzing yeast Top2 SUMO conjugates in vivo.

Analyzing Top2 distribution on yeast chromosomes by chromatin immunoprecipitation.

In vertebrate cells, DNA topoisomerase II (Topo II), named Top2 in yeast, localizes along chromosome axes early in mitosis and concentrates within centromeric chromatin during metaphase. The factors controlling these changes in enzyme distribution are largely unknown. Insight into Topo II dynamics could potentially be derived through genetic approaches in yeast. In practice, however, the small size and limited compaction of yeast chromosomes has precluded a detailed analysis of Top2 localization along mitotic chromosomes. As an alternative approach, we describe a method for examining Top2 distribution using chromatin immunoprecipitation (ChIP). By adding a detergent solubilization step, this method allows efficient recovery of DNA sequences associated with Top2 in the insoluble chromosome scaffold fraction.

The yeast SUMO isopeptidase Smt4/Ulp2 and the polo kinase Cdc5 act in an opposing fashion to regulate sumoylation in mitosis and cohesion at centromeres.

Post-translation modification through the SUMO pathway is cell cycle regulated, with specific SUMO conjugates accumulating in mitotic cells. The basis for this regulation, however, and its functional significance remain poorly understood. We present evidence that in budding yeast sumoylation during mitosis may be controlled through the SUMO deconjugating enzyme Smt4/Ulp2. We isolated the polo kinase Cdc5 as an Ulp2-interacting protein, and find a C-terminal region of Ulp2 is phosphorylated during mitosis in a Cdc5-dependent manner. cdc5 mutants display reduced levels of mitotic SUMO conjugates, suggesting Cdc5 may negatively regulate Ulp2 to promote sumoylation. Previously, we found one phenotype associated with ulp2 mutants is an inability to maintain chromatid cohesion at centromere-proximal chromosomal regions. We now show this defect is rescued by inactivating Cdc5, indicating Ulp2 maintains cohesion by counter-acting Cdc5 activity. The cohesinregulator Pds5 is a likely target of this pathway, as Cdc5 overproduction forces Pds5 dissociation from chromosomes and Pds5 overproduction restores cohesion in ulp2 mutants. Overall, these observations reveal Cdc5 is a novel regulator of the SUMO pathway and suggest the outlines of a broader circuitry in which Ulp2 and Cdc5 act in a mutually antagonistic fashion to modulate maintenance and dissolution of cohesion at centromeres.